Laboratory-based surveillance of chronic kidney disease in people with private health coverage in Brazil

Background Although approximately 25% of Brazilians have private health coverage (PHC), studies on the surveillance of chronic kidney disease (CKD) in this population are scarce. The objective of this study was to estimate the prevalence of CKD in individuals under two PHC regimes in Brazil, who total 8,335,724 beneficiaries. Methods Outpatient serum creatinine and proteinuria results of individuals from all five regions of Brazil, ≥ 18 years of age, and performed between 10/01/2021 and 10/31/2022, were analyzed through the own laboratory network database. People with serum creatinine measurements were evaluated for the prevalence and staging of CKD, and those with simultaneous measurements of serum creatinine and proteinuria were evaluated for the risk category of the disease. CKD was classified according to current guidelines and was defined as a glomerular filtration rate (GFR) < 60 ml/min/1.73 m² estimated by the 2021 CKD-EPI equation. Results The number of adults with serum creatinine results was 1,508,766 (age 44.0 [IQR, 33.9–56.8] years, 62.3% female). The estimated prevalence of CKD was 3.8% (2.6%, 0.8%, 0.2% and 0.2% in CKD stages 3a, 3b, 4 and 5, respectively), and it was higher in males than females (4.0% vs. 3.7%, p < 0.001, respectively) and in older age groups (0.2% among 18-29-year-olds, 0.5% among 30-44-year-olds, 2.0% among 45-59-year-olds, 9.4% among 60-74-year-olds, and 32.4% among ≥ 75-year-olds, p < 0.001) Adults with simultaneous results of creatinine and proteinuria were 64,178 (age 57.0 [IQR, 44.8–67.3] years, 58.1% female). After adjusting for age and gender, 70.1% were in the low-risk category of CKD, 20.0% were in the moderate-risk category, 5.8% were in the high-risk category, and 4.1% were in the very high-risk category. Conclusion The estimated prevalence of CKD was 3.8%, and approximately 10% of the participants were in the categories of high or very high-risk of the disease. While almost 20% of beneficiaries with PHC had serum creatinine data, fewer than 1% underwent tests for proteinuria. This study was one of the largest ever conducted in Brazil and the first one to use the 2021 CKD-EPI equation to estimate the prevalence of CKD. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-024-03597-9.


Background
Chronic kidney disease (CKD) is a major global public health problem, as a common condition that is silent in its early stages, preventable, neglected in many places and costly for all health systems [1].In developed countries, more than 10% of adults have some degree of CKD, and most of this prevalence is increasing [2].The complications of CKD can be avoided or mitigated with adequate care, and screening and early treatment are cost-effective in the population at risk [3,4].Nations with universal health insurance coverage have 5-7% of their budgets consumed by kidney replacement therapy, which is the final phase of care for CKD [5].Nevertheless, CKD is not a subject of the prioritized programs to combat chronic noncommunicable diseases (NCDs) in many countries, including Brazil [6].Between 2008 and 2023, the expenditures of the Brazilian Unified Health System (SUS) on outpatient kidney replacement therapy increased from approximately 1.7 to 4.1 billion Brazilian reais (nearly 340 to 820 million US dollars) [7].
Only in theory does Brazil have clinical guidelines for comprehensive care of patients with CKD and specific ministerial ordinance for the operation of health services relevant to this care [8,9].In fact, national studies have shown several inadequacies in the early identification of CKD by primary health care and in the population's access to consultations with a nephrologist and to CKD diagnosis and follow-up tests [10,11].Despite these gaps that are highly present in the Brazilian scenario, this country is one of the few places in the world with universal coverage for dialysis and kidney transplantation [12,13].Among the public health actions relevant to the secondary prevention of CKD, epidemiological surveillance stands out, especially given the asymptomatic nature of the early stages of this disease and that many of the traditional nephroprotective medications are low-cost and covered by SUS [14][15][16].
Brazil is a country with a dual health care system in which the public health care system coexists with private health care.Approximately 25% of the Brazilian population has PHC [17].However, detailed information on programs to combat NCD or care for complex patients in private health care is scarce [18].The objective of this study was to estimate the prevalence of CKD in individuals with PHC in Brazil.

Study design and population
This was a retrospective, cross-sectional study based on records of laboratory tests performed between 10/01/2021 and 10/31/2022 in the own laboratory network of two private health companies in Brazil.Together, these companies are national in scope and have a medical assistance portfolio consisting of approximately 8,335,724 beneficiaries [19].Outpatient serum creatinine and proteinuria tests of individuals from all five regions of Brazil were analyzed.This country has 26 states, in addition to the federal district, and is divided into five large regions (Fig. 1).The exclusion criteria were tests from patients under 18 years of age and those performed in hospital and emergency settings.
The study adhered to the Declaration of Helsinki and Resolution 466/2012 of the Brazilian National Health Council and was approved by the research ethics committee on 11/01/2022 under number 64260622.1.0000.8098.The free and informed consent form was waived because the study was observational, retrospective, noninterventional and large, making it impossible to communicate with all participants.The extraction of information from the database of the laboratories occurred between 12/01/2022 and 04/13/2023.

Data source, variables, and definitions
Demographic data of the participants (age, gender and collection site) and results of serum creatinine and urinary protein were obtained from laboratory records.In case of patients with two or more measurements of a given test, the lowest value available was used, to avoid overestimation of the prevalence and severity of CKD.
The representativeness of the sample in the regions of Brazil was calculated as the proportion between the number of adults who underwent the evaluated tests and the number of beneficiaries within each region.According to the historical series, the annual amount of serum creatinine tests performed is approximately 2,500,000, but the number of proteinuria measurements is less than 100,000.Therefore, patients with serum creatinine measurements were evaluated for the prevalence of CKD and its stages, and those with simultaneous serum creatinine and proteinuria measurements were evaluated regarding the risk of CKD.According to the CKD heat map of KDIGO 2012 Clinical Practice Guideline (Kidney Disease Improving Global Outcomes), patients were considered to be at low risk when they had GFR ≥ 60 ml/ min/1.73m² and mild proteinuria.They were at moderate risk when they had GFR ≥ 60 ml/min/1.73m² and moderate proteinuria or GFR 45-59 ml/min/1.73m² and mild proteinuria.Patients were in the high-risk category for CKD when they had any of the following combinations: GFR ≥ 60 ml/min/1.73m² and severe proteinuria, GFR 45-59 ml/min/1.73m² and moderate proteinuria, or GFR 30-44 ml/min/1.73m² and mild proteinuria.They were at very high-risk when they had GFR 45-59 ml/ min/1.73m² and severe proteinuria, GFR 30-44 ml/ min/1.73m² and moderate or severe proteinuria, or GFR < 30 ml/min/1.73m² regardless of the level of proteinuria [21].

Data analysis
Initially, the distribution of participants by demographic variables (gender, age group, and region of Brazil) and laboratory results (GFR and proteinuria) was evaluated, and their respective 95% confidence intervals were calculated.The distribution of patients in the different GFR ranges was assessed according to gender, age, and region of Brazil.The intergroup distribution was assessed using the χ² test.The crude prevalence of CKD by region of Brazil was estimated as the proportion of the number of people with abnormal tests out of the total number of people who underwent that test.A risk map (or heat map) of CKD was drawn by crossing the GFR information and the proteinuria categories.Finally, the prevalence rates were adjusted for age and gender using the direct method, with the total study population as a reference.Statistical analyses were conducted using R version 4.2.1 software.

Results
Between 1 October 2021 and 31 October 2022, 3,520,678 serum creatinine measurements were recorded.After excluding tests performed in hospitals or emergency rooms (1,137,104), tests performed in people under 18 years of age (211,200), and duplicate tests (663,608), 1,508,766 adults were included for the estimation of CKD prevalence and staging.Among them, 64,178 (4.3%) had results of both serum creatinine and proteinuria, so this was the number evaluated for the risk categories of CKD (Fig. 2).
Patients with serum creatinine values made up 18.1% of the total beneficiaries of with PHC (20.2% in the North, 24.2% in the Northeast, 13.9% in the Midwest, 15.2% in the Southeast, and 19.6% in the South).Patients with both serum creatinine and proteinuria data were 0.8% of the beneficiaries (0.7% in the Northeast, 0.4% in the North, 1.7% in the South, 0.8% in the Southeast, and 0.6% in the Midwest) (Table 2).
The proportion of males with proteinuria was higher than that of females (26.08% versus 21.87%, p < 0.001).There was no progressive increase in the prevalence of proteinuria with age.The distribution of the total sample in levels of proteinuria was 76,37% at mild, 18.05% at moderate, and 5.58% at severe level (Table 5).
According to the CKD risk map, the crude prevalence of patients with low, moderate, high and very high-risk categories for the disease was 68.9%, 19.4%, 6.6% and 5.1%, respectively.After adjusting for age and gender, these prevalences were: 70.1%, 20.0%, 5.8% and 4.1%, respectively (Fig. 4).

Discussion
The present study showed that the prevalence of CKD in beneficiaries with PHC in Brazil was 3.8%, according to the GFR estimated by the 2021 CKD-EPI equation.After adjusting for age and gender, this prevalence was higher in the Midwest and Southeast and lower in the North and Northeast of Brazil.While 18.1% of the beneficiaries were tested for serum creatinine, only 0.8% underwent measurement of proteinuria.Among them, approximately 10% were at high or very high-risk categories of CKD.
In recent decades, several studies have estimated the prevalence of CKD (Table 6 S) .The great variability of results (0.8-32.5%) is due, among other factors, to the population profile (age, comorbidities), the data sources (telephone survey, disease codes, screening programs, population-based studies, laboratory databases), and the definitions of CKD used (reduced GFR with or without altered proteinuria).
The estimated prevalence of CKD of 3.8% found in the present study was higher than that found in studies based on telephone surveys (1.4%) [22,41] and by registering disease codes (0.8%) [29].This might have been due to the silent nature of the early stages of CKD, which leads to low awareness among the population about the disease and identification failures of it by health professionals [35].This fact reinforces the need for screening for CKD in people at risk by measuring serum creatinine and proteinuria [8,9,21].
On the other hand, our prevalence of 3.8% was lower than the estimates of CKD prevalence from screening programs (8.9-32.5%),which generally include individuals with risk factors for the disease, such as hypertension, diabetes mellitus, and cardiovascular diseases [25,26,28,33,35,36,38,39]. Another explanation for the lower prevalence of CKD found in this study might be the fact that we enrolled individuals with PHC, who might have a lower age and burden of comorbidities and better socioeconomic conditions, since they are mostly economically  active people with a corporate-type PHC.Unfortunately, detailed information on the comorbidity profile of our population was not available.
When compared to studies based on disease code registration and screening programs, it is possible that population-based studies [342, 37,40,42,43] and those based on laboratory databases [23,24,27,[29][30][31][32]44] can include individuals with lower disease burdens.Even so, the prevalence of CKD found in this study (3.8%) was lower than that in previous studies of the same nature (5.6-12.4%).Possible explanations would be the lower mean age of the participants in our study and the use of the 2021 CKD-EPI equation rather than the 2009 equation.In fact, older age is an important risk factor for reduced GFR, and the  2021 CKD-EPI equation may overestimate the GFR by 3-5 ml/min/1.73m² when compared to the 2009 CKD-EPI Eqs.[21,45,46].In our population, when the 2009 CKD-EPI equation was applied, the prevalence of CKD was estimated at 5.1% (Table 7 S).In addition, the definition of CKD used in this study considered only reduced GFR, as a very small proportion of people in Brazil are routinely tested for proteinuria.This fact constitutes a serious flaw in the implementation of the line of care for CKD in our country, which has already been pointed out by previous national studies [10,11].Thus, participants with preserved GFR and present proteinuria were not counted as having CKD.
In our study, the estimated prevalence of CKD was slightly higher in males than in females.On this matter, the previous reports show discordant results.Women could have more CKD than men due to their smaller nephron mass and greater chance of early diagnosis, since in many cultures women are more conscientious about their health than men [23, 25, 28, 31-33, 37, 43-45, 47-49].On the other hand, men might have a higher prevalence of CKD due to their higher frequency of hypertension and proteinuria [24,26,39].
The regional differences found after adjustment for age and gender could not be analysed in detail due to the unavailability of information on the patients' morbidities.It might be that individuals from the North and Northeast regions of Brazil have a lower prevalence of CKD due to the lower prevalence of hypertension, diabetes, and obesity, as shown in a national telephone survey [50].
The result of 24% of patients with proteinuria and 10% of patients at high or very high-risk categories of CKD found in this cohort is higher than the estimative of previous studies [10,35].Possibly patients of our study with proteinuria test requests were sicker than the population with serum creatinine dosages.In fact, the crude prevalence of high or very high-risk categories of CKD was higher than the age-and gender adjusted prevalence.Some limitations of this study should be acknowledged, such as the unavailability of information on the participants' comorbidities, the impossibility of using two serum creatinine results in the same individuals to confirm the diagnosis of CKD, and the noninclusion of proteinuria measurement in the assessment of the prevalence of CKD.Nevertheless, the importance of this study lies in its size (one of the largest ever conducted in Brazil), in the national representativeness of individuals with PHC (approximately one-fifth of the beneficiaries were tested for serum creatinine), and because it is the first Brazilian study to use the 2021 CKD-EPI equation to estimate the prevalence of CKD.

Conclusions
In this Brazilian national study of individuals with PHC, we found a prevalence of CKD of 3.8%, a deficiency of proteinuria screening, and approximately 10% of participants with high or very high-risk for such disease.These results provide relevant information on various strata of the Brazilian population with PHC and serve as a basis for planning interventions aimed at early diagnosis and care of CKD.

Fig. 2
Fig. 2 Flowchart of inclusion of study participants.CKD, chronic kidney disease.

Fig. 3
Fig. 3 Estimated prevalence of chronic kidney disease according to gender, age, and region of Brazil (n = 1,508,766)

Fig. 4
Fig. 4 Crude (A) and adjusted (B) distribution of patients according to the CKD risk map (n = 64,178)

Table 1
Characteristics of the patients included in the study CI, confidence interval.GFR, estimated glomerular filtration rate

Table 2
Representativeness of the sample, according to the region of Brazil

Table 3
Distribution of patients in estimated glomerular filtration rate ranges according to gender, age, and region of Brazil (n = 1,508,766)

Table 4
Median crude and adjusted CKD prevalence estimates by region of Brazil (n = 1,508,766) ¹ Median (interquartile)² Adjusted for age and gender, using the total number of participants as the standard population

Table 5
Distribution of patients in levels of proteinuria according to gender, age and region of Brazil (n = 64,178)